Total Synthesis of the Marine Antibiotic Pestalone and its Surprisingly Facile Conversion into Pestalalactone and Pestalachloride A

Abstract

Surprise, surprise! The total synthesis of the marine natural product pestalone (1), a highly substituted benzophenone with strong antibiotic acitivity, has provided insight into the surprising tendency of this and related molecules to undergo intramolecular Cannizzaro–Tishchenko‐type reactions. Pestalone can be readily converted into pestalachloride A, a strongly antifungal metabolite isolated from an endophytic fungus, by simple treatment with ammonia at pH 8.

Total Syntheses of Graphisin A and Sydowinin B

“…In our initial studies, we have targeted the highly functionalized, tetra- ortho -substituted benzophenone graphisin A 6 ( 4 ) and the corresponding cyclized xanthone sydowinin B 7 ( 5 ). Herein, we report the total synthesis of the highly substituted benzophenone 8 graphisin A using a suitably functionalized benzophenone as well as preparation of the derived xanthone sydowinin B via dehydrative cyclization.…”

New Metabolites and Bioactive Chlorinated Benzophenone Derivatives Produced by a Marine-Derived Fungus Pestalotiopsis heterocornis

“…Compounds 3 , 6 – 8 were identified as gamahorin ( 3 ) [15], pestalachloride B ( 6 ) [16], pestalachloride E ( 7 ) [17] and a mixture of pestalalactone atropisomers ( 8a / 8b ) [18,19] by comparison of the 1 H NMR, 13 C NMR and mass spectroscopy MS data with those reported.…”

“…Four new compounds, including two isocoumarins, pestaloisocoumarin A ( 1 ) and pestaloisocoumarin B ( 2 ), one sesquiterpenoid degradation, isopolisin B ( 4 ), and one furan derivative, pestalotiol A ( 5 ), together with four known compounds, gamahorin ( 3 ) [15], pestalachloride B ( 6 ) [16], pestalachloride E ( 7 ) [17] and a mixture of pestalalactone atropisomers ( 8a/8b ) [18,19], were discovered (Figure 1). The structures of the new compounds were elucidated on the basis of spectroscopic data, circular dichroism (CD) Cotton effects and single-crystal X-ray crystallographic analysis.…”

The chemistry of isoindole natural products

“…The reaction of 192 with an equivalent of ammonia gives a cyclic iminohemiaminal, which first tautomerizes to the hydroxy isoindole and then to the isoindolinone 193 . This biosynthetic transformation was also used in the total synthesis of 193 by Schmalz (Scheme 24) [149]. Reaction of lithiated 188 (three steps from commercially available 5-methylresorcinol) with the aldehyde 189 (double bromination of 3,5-dimethoxybenzaldehyde) gave the racemic alcohol 190 .…”